Gender Differences, Gamma Phase Synchrony and Schizophrenia

When considering the question "Gender: Does It Make a Difference?" the simple answer is yes-men and women do appear to experience schizophrenia differently. Over the past few decades, gender differences in the epidemiology and brain morphology of patients with schizophrenia have become increasingly more clear (for a concise analysis, see Castle et al., 2000). While these investigations have allowed researchers to learn more about the disorder of schizophrenia, studies looking at gender differences at the functional level remain lacking. Contemporary models of schizophrenia postulate that the core pathophysiology of the disorder is an abnormal temporal integration of brain networks or cognitive dysmetria (Andreasen et al., 1999). Given this assumption, our aim has been to investigate gender differences in patients with schizophrenia at the highest temporal resolution window of synchronous 40 Hz gamma event-related potential (ERP) activity.

Gender Research

Investigators have identified significant gender differences in the epidemiology of schizophrenia. It is now accepted that women with schizophrenia have a considerably less severe course of illness exhibited by fewer hospitalizations, shorter inpatient stays and better social adaptation compared to men (Tamminga, 1997). Research of the premorbid functioning in patients with schizophrenia has confirmed that young women perform better than young men in areas of social functioning, cognitive functioning and academic achievement (Lewine, 1981; Mueser et al., 1990). Gender differences in psychopathology have also been found, with women tending to have more mood features and fewer negative symptoms (Childers and Harding, 1990; Kulkarni, 1997). Comorbid substance abuse also appears to be gender-mediated, with more men abusing drugs and alcohol, in accordance with the general population (De Quardo et al., 1994). Finally, a difference in the age of onset between men and women with schizophrenia has also been identified, with the illness manifesting at a later age in women than in men (Castle and Murray, 1993; Faraone et al., 1994).

The other main area of gender research in schizophrenia has focused on brain morphology. Historically, most studies in this area have concentrated on the normal population. Findings have ranged from the well-documented-a substantially larger average size male brain (Lynn, 1994)-to the more detailed-females have proportionally larger Wernicke and Broca language-associated regions than males (Harasty et al., 1997). Investigators have also found a higher density of neurons in the orbital area of the female brain (Haug, 1984) and a consistently greater amount of right-left asymmetry in the planum temporale of male controls (Wada et al., 1975). The corpus callosum-the major fiber tract connecting the two hemispheres-has also been found to display sexually different dimorphism. Post-mortem studies have found that the total area of the absolute size of the corpus callosum was larger in females and that women have a more rounded and bulbous splenium of the corpus callosum (Holloway et al., 1993).

Investigations that have looked at brain structural abnormalities in patients with schizophrenia have primarily concentrated on measures of ventricular enlargement. Although there are conflicting findings, most studies have found that males with schizophrenia have a higher ventricular-brain ratio compared to females (Nopoulos et al., 1997; Flaum et al., 1990).

Of particular relevance to our hypothesis is the research into gender differences of the corpus callosum within the population with schizophrenia. While there have been numerous investigations, most have tended to look at the difference between patients with schizophrenia and controls without taking into account gender differences. One exception is a study by Nasrallah et al. (1986), which found that females with schizophrenia (relative to controls) manifested an increased thickness at the anterior and middle sections of the corpus callosum.